PB2266: TRIAL IN PROGRESS: PHASE 3 TRIAL OF ODRONEXTAMAB PLUS LENALIDOMIDE VERSUS RITUXIMAB PLUS LENALIDOMIDE IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AND MARGINAL ZONE LYMPHOMA (OLYMPIA-5)
Authors: Umberto Vitolo, Elizabeth H. Phillips, Aránzazu Alonso Alonso, Michele Merli, Ashish Risal, Manjusha Namuduri, Biyi Shen, Dina Flink, Min Zhu, Sushmita Mukherjee, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Raul Cordoba
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are types of indolent B-cell non-Hodgkin lymphoma (B-NHL). Patients (pts) with relapsed/refractory (R/R) FL or MZL are treated in a similar way. Despite the efficacy observed with rituximab-lenalidomide (R2) in the treatment of pts with R/R FL and to a lesser extent in MZL, a significant proportion of pts fail to achieve an optimal and durable response. Odronextamab is an off-the-shelf CD20×CD3 bispecific antibody. In the Phase 1 ELM-1 study, odronextamab monotherapy showed antitumor activity in a range of R/R B-NHL subtypes, including FL and MZL. Odronextamab had a generally manageable safety profile with infrequent treatment-emergent adverse events leading to treatment discontinuation (8%) (Bannerji, et al. Lancet Haematol. 2022). In the Phase 2 ELM-2 study, odronextamab elicited an objective response rate of 82% and complete response (CR) rate of 75% in pts with heavily pre-treated R/R FL who received ≥2 prior lines of therapy (Kim, et al. ASH, 2022). These positive data support evaluation of odronextamab in R/R FL and MZL in earlier lines of therapies. Combining odronextamab with lenalidomide has the potential to improve efficacy in the R/R setting compared with R2. Aims: To evaluate the efficacy and safety of odronextamab plus lenalidomide versus R2 in pts with R/R FL and MZL. Methods: OLYMPIA-5 is a Phase 3, open-label, randomized trial of odronextamab plus lenalidomide versus R2 in R/R FL and MZL. In Part 1 (safety run-in in R/R FL), odronextamab and lenalidomide are administered for twelve 28-day cycles or until relapse, progressive disease, withdrawal of consent, or unacceptable toxicity. Odronextamab intravenous infusion is administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, with a full dose to be administered from C2. In Part 2 (randomization), pts with R/R FL or MZL will be randomized in 1:1 fashion to receive either 12 cycles of odronextamab plus lenalidomide or R2 where rituximab and lenalidomide will be administered for the first 5 cycles following which lenalidomide monotherapy will continue from C6–12 as standard schedule (Leonard JP, et al. J Clin Oncol. 2019). Pts aged ≥18 years with histologically confirmed FL Grade 1–3a or MZL (nodal, splenic, or extra nodal) who have refractory disease or relapsed after ≥1 prior systemic therapy that included ≥1 anti-CD20 antibody are eligible. Patients also need to have measurable disease and Eastern Cooperative Oncology Group Performance Status 0–2. Exclusion criteria include central nervous system (CNS) lymphoma, history of or current relevant CNS pathology, and histological evidence of transformation to high-grade or diffuse large B-cell lymphoma. Pts with prior use of lenalidomide or any CD20×CD3 bispecific antibody within 6 months are also excluded. Results: The primary endpoint is progression-free survival as assessed by independent central review, with key secondary endpoints of CR, best overall response, and overall survival. Biomarker analysis will be performed. An estimated 200 sites globally will participate to enroll approximately 24–48 pts in Part 1 and 422 pts in Part 2 (352 R/R FL and 70 R/R MZL). Summary/Conclusion: This Phase 3 trial will determine the efficacy and safety of odronextamab plus lenalidomide compared with R2 in patients with R/R FL and MZL.Keywords: Phase III, Bispecific, Non-Hodgkin’s lymphoma, Follicular lymphoma